Determination of treatment modalities for diabetic retinopathy and diabetic maculopathy -Strategic approach using molecular and cellular biological methods-

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Various factors are involved in the pathogenesis of diabetic retinopathy and diabetic maculopathy (macular edema). The candidates of the risk factors are factors related to oxidative stress and retinal angiogenesis. As the first step, to investigate the candidate molecules to play important roles in diabetic retinopathy, the expression levels of the bio-marker of cell damage due to oxidative stress ((8-OHdG and NOx) and cytokines (VEGF and IL-6) were measured in the vitreous humor obtained from the diabetic eyes after securing the written permission. This study was approved by the ethical committee of Yamagata University Faculty of Medicine. This study has revealed that the diabetic retinopathy and the diabetic maculopathy are closely related to the oxidative stress and VEGF, IL-6. As the second step, to investigate the molecular pathogenesis of diabetic retinopathy by focusing the retinal damage to retinal neurons, the intracellular signal transduction of hyperglycemia, including abno … More rmal metabolic pathways and cytokine expression acceleration, has been investigated using the in vitro systems. This study has revealed that diacylglycerol activates protein kinase C, which increases VEGF expression in retinal cells.Taken together, VEGF is one of the main factors to be involved in the pathogenesis of diabetic retinopathy and maculopathy. One of the single nucleotide polymorphisms (SNPs) in the VEGF gene was investigated. The frequencies of VEGF +813 C-T (CC, CT, TT) were determined in DNA from 108 subjects (non DM=12 subjects, DM=96 subjects). The frequencies of the VEGF +813 C_T polymorphisms were similar in both DM and non DM groups. The severity of retinopathy was not related to VEGF +813 polymorphism. The results of this study have revealed that the expression levels of cytokines and oxidative stress related factors, not the genetic factor were related to diabetic retinopathy and maculopathy. It is mandatory to search for the more useful factors relevant to diabetic retinopathy and maculopathy to set up the system to determine the treatment modalities for diabetic retinopathy and maculopathy. Less